We are currently carrying out a prospective epidemiologic study of type II diabetes and its microvascular complications in low-income residents of Mexico City. A 3.25 year followup examination (FU1) of a cohort of 2258 Mexican men and women, ages 35-64 years at baseline, has now been completed. We propose to study the natural history of diabetes and its macrovascular complications by re-examining this cohort at 3.25-year intervals (6.5 years (FU2) and 9.75 years (FU3) after baseline). We postulate that different risk factors will prevail in the early (more than 3.25 years prior to conversion to diabetes) than in the late (3.25 years or less prior to conversion) prediabetic period. We hypothesize that in the early prediabetic period risk factors associated with the Insulin Resistance Syndrome will predominate, i.e., high "specific" insulin concentration (measured by a specific immunoassay), hypertriglyceridemia, low HDL-cholesterol, and hypertension, whereas in the late prediabetic period factors associated with insulin secretory failure, i.e., increased proinsulin and low "specific" insulin, will predominate. We assessed carotid wall thickness by ultrasonography on all subjects at FU1 and plan to repeat this at FU2. We will measure advanced glycation endproduct (AGE)-modified apolipoprotein B and a panel of inflammatory risk factor (serum albumin, serum amyloid A, alpha1-acid glycoprotein, and C- reactive protein) on stored contingency specimens from baseline and FU1 in order to determine if these factors predict accelerated thickening of carotic walls and/or the development of type II diabetes. We will also quantify the extent to which carotid wall thickness and ECG documented myocardial infarction precede clinical diabetes as predicted by the "common soil" hypothesis, i.e., the hypothesis that both type II diabetes and atherosclerosis have common genetic and environmental antecedents.